miR-542-5p targets GREM1 to affect the progression of renal fibrosis.

Renal fibrosis (RF) is a typical pathological presentation of end-stage chronic kidney disease (CKD) and autosomal dominant polycystic kidney disease (ADPKD). However, the precise regulatory mechanisms governing this re-expression process remain unclear. Differentially expressed microRNAs (miRNAs) associated with RF were screened by microarray analysis using the Gene Expression Omnibus (GEO) database. The miRNAs upstream of the genes in question were predicted using the miRWalk database. The miRNAs involved in the two GEO data sets were intersected to identify key miRNAs; their regulatory pathways were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Subsequently, the effects and the underlying mechanisms of target miRNA on RF were examined in a unilateral ureteral obstruction (UUO)-induced mice renal fibrotic model and a transforming growth factor-ß1 (TGF-ß1)-induced tubular epithelium (HK-2) fibrotic cell model. In total, 109 and 32 differentially expressed miRNAs were identified in the GSE133530 and GSE80247 data sets, respectively. GREM1 was identified as a hub gene, where its 2196 upstream miRNAs were predicted; miR-574-5p was found to be downregulated and closely related to fibrosis after data set intersection and enrichment analyses, thus was selected for further investigation. A differential expression heatmap (GSE162794) showed that miR-542-5p was downregulated. The expression of GREM1 mRNA was upregulated, whereas that of miR-542-5p was downregulated in UUO mice and fibrotic HK-2 cells as compared with the relevant controls. The binding site of miR-542-5p was predicted at the 3'UTR region of GREM1 and was confirmed by subsequent dual luciferase reporter gene assay. Western blot analysis showed that Gremlin-1 and Fibronectin were significantly upregulated after induction of TGF-ß1; when miR-542-5p was overexpressed or GREM1 mRNA was interfered, the upregulations of Gremlin-1 and Fibronectin were significantly reduced. Our research demonstrates that miR-542-5p plays a critical role in the progression of RF, and thus may be a promising therapeutic target for CKD and ADPKD.

The value of bronchodilator response in FEV1 and FeNO for differentiating between chronic respiratory diseases: an observational study.

BACKGROUND: There is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result. METHODS: Three standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study. RESULTS: The rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83-0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was < 315 mL combined with FeNO < 28.5 parts per billion, patients with a positive BDT result were more likely to have pure COPD (AUC: 0.774; 95% CI 0.72-0.83). CONCLUSION: The simplified standard II can replace standard I. ΔFEV1 and FeNO are helpful in differentiating between asthma, COPD, and ACO in patients with a positive BDT result.

Inhibition of xanthine oxidase by allopurinol suppresses HMGB1 secretion and ameliorates experimental asthma.

BACKGROUND: Extracellular high mobility group box 1 (HMGB1) is a key mediator in driving allergic airway inflammation and contributes to asthma. Yet, mechanism of HMGB1 secretion in asthma is poorly defined. Pulmonary metabolic dysfunction is recently recognized as a driver of respiratory pathology. However, the altered metabolic signatures and the roles of metabolic to allergic airway inflammation remain unclear. METHODS: Male C57BL/6 J mice were sensitized and challenged with toluene diisocyanate (TDI) to generate a chemically induced asthma model. Pulmonary untargeted metabolomics was employed. According to results, mice were orally administered allopurinol, a xanthine oxidase (XO) inhibitor. Human bronchial epithelial cells (16HBE) were stimulated by TDI-human serum albumin (HSA). RESULTS: We identified the purine metabolism was the most enriched pathway in TDI-exposed lungs, corresponding to the increase of xanthine and uric acid, products of purine degradation mediated by XO. Inhibition of XO by allopurinol ameliorates TDI-induced oxidative stress and DNA damage, mixed granulocytic airway inflammation and Th1, Th2 and Th17 immunology as well as HMGB1 acetylation and secretion. Mechanistically, HMGB1 acetylation was caused by decreased activation of the NAD+-sirtuin 1 (SIRT1) axis triggered by hyperactivation of the DNA damage sensor poly (ADP-ribose)-polymerase 1 (PARP-1). This was rescued by allopurinol, PARP-1 inhibitor or supplementation with NAD+ precursor in a SIRT1-dependent manner. Meanwhile, allopurinol attenuated Nrf2 defect due to SIRT1 inactivation to help ROS scavenge. CONCLUSIONS: We demonstrated a novel regulation of HMGB1 acetylation and secretion by purine metabolism that is critical for asthma onset. Allopurinol may have therapeutic potential in patients with asthma.

Urinary SPP1 has potential as a non-invasive diagnostic marker for focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a type of chronic glomerular nephropathy showing characteristic glomerular sclerosis, diagnosed by kidney biopsy. However, it is difficult and expensive to monitor disease progression with repeated renal biopsy in clinical practice, and thus here we explored the feasibility of urine biomarkers as non-invasive diagnostic tools. We downloaded scRNA-seq datasets of 20 urine cell samples and 3 kidney tissues and obtained two gene lists encoding extracellular proteins for bioinformatic analysis; in addition, we identified key EP-Genes by immunohistochemical staining and performed bulk RNA sequencing with 12 urine samples. We report that urine cells and kidney cells were correlated. A total of 64 EP-Genes were acquired by intersecting genes of distal tubular cluster with extracellular proteins. Function enrichment analysis showed that EP-Genes might be involved in the immune response and extracellular components. Six key EP-Genes were identified and correlated with renal function. IMC showed that key EP-Genes were located mainly in tubules. Cross verification and examination of a urine RNAseq dataset showed that SPP1 had diagnostic potential for FSGS. The presence of urine SPP1 was primarily associated with macrophage infiltration in kidney, and the pathogenesis of FSGS may be related to innate immunity. Urinary cells seemed to be strongly similar to kidney cells. In summary, SPP1 levels reflect renal function and may have potential as a biomarker for non-invasive diagnosis of FSGS.

Effect of granulation on chlorine-release behavior during municipal solid waste incineration.

The preparation of refuse-derived fuel (RDF) is an effective and simple means of rural municipal solid waste utilization. The release of chlorine during RDF combustion is important as it causes high-temperature corrosion and pollutants emission such as HCl, dioxins, etc. In this paper, constant-temperature and increasing-temperature combustion experiments were carried out using an electrically heating furnace to analyse the effects of granulation (pressure and additives) on the release of chlorine in particles. During the constant-temperature combustion below 800 °C, only organic chlorine was released from the RDF. The increase of granulation pressure from 1 MPa to 10 MPa did not affect the total amount of chlorine release, but delayed the organic chlorine release by increasing the gas diffusion resistance. During the constant-temperature combustion above 900 °C, inorganic chlorine was released as well. The increase of granulation pressure enhanced the inorganic chlorine release significantly by promoting the reactants contact. During the increasing-temperature combustion, the increase of granulation pressure delayed the organic chlorine release as well but inhibited the inorganic chlorine release. This was mainly attributed to the slow temperature rise to 900 °C, during which the inherent calcium in the RDF reacted with silicon and aluminium, resulting in less reactants for an inorganic chlorine release reaction. Three calcium-based additives were used to inhibit chlorine release. CaCO3 showed no dechlorination effect, and CaO showed better dechlorination effect than Ca(OH)2. For the constant-temperature combustion at 900 °C, the addition of CaO with a Ca/Cl ratio of 2 achieved a dechlorination efficiency of over 90%, with little influence from the granulation pressure. For the increasing-temperature combustion, the granulation pressure had a significant influence on CaO dechlorination effectiveness. Only at a granulation pressure as high as 10 MPa, did the addition of CaO with the Ca/Cl ratio of 2.5 achieve a dechlorination efficiency of 95%.

Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD.

Purpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD. Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor. Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-ß1 were decreased compared with UUO (P < 0.05). Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.

Experimental Investigation of Removal of SO3 from Flue Gas with Modified Fly Ash Adsorbents.

The removal of nonconventional pollutants in coal-fired power plants, such as SO3, has been receiving more and more attention. However, due to its unique nature, it is difficult to remove SO3 effectively with the widely used wet flue gas desulfurization systems. Nowadays, dry-sorbent injection technology has become a promising method for SO3 emission control in coal-fired power plants. The removal characteristics of SO3 from flue gas with modified fly ash adsorbents were investigated in a fixed-bed reactor. Factors affecting the adsorption efficiency of SO3 were studied, including modification method, modified fly ash adsorbent particle size, reaction temperature, and flue gas component. Combined with adsorbent characterization analysis, the adsorption kinetics of SO3 by modified fly ash adsorbents were carried out with four different adsorption kinetics models. The results show that the SO3 adsorption efficiency of the fly ash samples increases after modification; the best SO3 removal performance of fly ash was achieved when 1.5 mol/L NaOH solution was used, with the highest SO3 adsorption efficiency of up to 98.3%. The modified fly ash adsorbent particle size, water vapor content, and the addition of NO have little effect on the adsorption efficiency of SO3. As the reaction temperature increases from 250 to 450 °C, the SO3 adsorption efficiency first increases and then decreases, with an optimal reaction temperature of 350 °C. The addition of SO2 would compete with SO3 for adsorption and inhibit the uptake of SO3 by the adsorbent. Adsorption kinetics data show that external mass transfer and chemical adsorption are the main critical mechanisms affecting the adsorption efficiency of the modified fly ash adsorbent in the SO3 removal process compared to internal diffusion.

Different ratios of DHA/EPA reverses insulin resistance by improving adipocyte dysfunction and lipid disorders in HFD-induced IR mice.

Objective: Insulin resistance (IR) is linked to the development of diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVDs). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fish oils (FOs) were used to investigate their potential in high-fat diet (HFD)-induced IR mice under different ratios. Methods: A total of 84 male C57BL/6J (6 weeks old) mice were fed with HFD containing 45% kcal from fat for 16 weeks to establish the IR model. The IR mice were then fed with HFD or HFD + 4% DHA/EPA with different ratios (3 : 1, 1.5 : 1, 1 : 1, 1 : 1.5, 1 : 3, respectively) for another 12 weeks. During the experiment, the CON group (n = 12) was set to feed with a basic diet containing 10% kcal from fat. Results: HFD feeding for 16 weeks reduced insulin sensitivity and accelerated hypertrophy of white adipose tissue (WAT). Different ratios of DHA/EPA except for 1 : 1 decreased the HOMA-IR index, average area of adipocytes, and serum MDA, but increased the protein expression of PI3K. All ratios of DHA/EPA increased the protein expression of IRS-1, GLUT4, and adiponectin. Moreover, dietary DHA/EPA changed serum fatty acid (FA) composition by increasing the serum concentration of n-3 PUFAs. DHA/EPA supplements also improved serum lipid profiles (TG/TC/LDL-c/HDL-c, FFA) and reduced the hepatic steatosis area. Conclusions: The results indicate that an appropriate higher ratio of DHA (1.5 : 1) in DHA/EPA supplementation is recommended for IR prevention.

Urinary PART1 and PLA2R1 Could Potentially Serve as Diagnostic Markers for Diabetic Kidney Disease Patients.

Background: Diabetic kidney disease (DKD) is a chronic renal disease which could eventually develop into renal failure. Though albuminuria and estimated glomerular filtration rate (eGFR) are helpful for the diagnosis of DKD, the lack of specific biomarkers reduces the efficiency of therapeutic interventions. Methods: Based on bulk-seq of 56 urine samples collected at different time points (including 11 acquired from DKD patients and 11 from healthy controls), in corporation of scRNA-seq data of urine samples and snRNA-seq data of renal punctures from DKD patients (retrieved from NCBI GEO Omnibus), urine-kidney specific genes were identified by Multiple Biological Information methods. Results: Forty urine-kidney specific genes/differentially expressed genes (DEGs) were identified to be highly related to kidney injury and proteinuria for the DKD patients. Most of these genes participate in regulating glucagon and apoptosis, among which, urinary PART1 (mainly derived from distal tubular cells) and PLA2R1 (podocyte cell surface marker) could be used together for the early diagnosis of DKD. Moreover, urinary PART1 was significantly associated with multiple clinical indicators, and remained stable over time in urine. Conclusion: Urinary PART1 and PLA2R1 could be shed lights on the discovery and development of non-invasive diagnostic method for DKD, especially in early stages.

Enhanced degradation of DDT using a novel iron-assisted hydrochar catalyst combined with peroxymonosulfate: Experiment and mechanism analysis.

Poplar wood (PW) hydrochar modified by iron (Fe@HC) was prepared greenly by one-step hydrothermal method. The adsorption and degradation performance of DDT was investigated in a heterogeneous advanced oxidation system (Fe@HC/PMS) formed by Fe@HC collaborated with peroxymonosulfate (PMS). The effects of Fe@HC dosage, PMS dosage and DDT initial concentration were quantitatively analyzed. The results showed that DDT removal efficiency can reach to 88.62% in 240 min under optimal conditions (4 g/L Fe@HC, 10 mM PMS, 0.5 mg/L DDT, 5.5 pH0) in Fe@HC/PMS system. Furthermore, Fe@HC/PMS system exhibited high degradation rate and TOC removal efficiency for the removal of various organic contaminants. The influence mechanisms of Fe@HC/PMS system on DDT adsorption and degradation were proposed based on electron paramagnetic resonance (EPR) testing analysis and radical quenching experiments. Based on the mechanism analysis, the influence of Fe@HC/PMS on DDT removal efficiency can be concluded in the order: Active substance indirect degradation (60.95%) > Fe@HC direct degradation (10.13%) > Fe@HC adsorption (17.54%). Among active substance indirect degradation, SO4•-, •OH, O2•- and 1O2 occupied 27.56%, 15.74%, 5.33% and 12.32%, respectively. Moreover, DDT degradation intermediates were detected by a gas chromatography-mass spectrometer (GC-MS) to predict DDT degradation pathways. This study provided a green progress for the reuse of biomass resources and a new way for the enhanced degradation of DDT.

Effects of nitrogen application rate on the photosynthetic pigment, leaf fluorescence characteristics, and yield of indica hybrid rice and their interrelations.

A field experiment employing the rice cultivars Qyou6 and Yixiangyou2115 as materials and different nitrogen application rates was conducted in Huangping County, Guizhou Province in 2019 to determine the effects of nitrogen application rate on photosynthetic pigments, leaf fluorescence characteristics, yield, and their interrelations in indica hybrid rice. The results showed that photosynthetic pigment contents generally increased with increasing nitrogen application rate. As the nitrogen rate increased, the maximal quantum yield of PSII (Fv/Fm), actual quantum yield of PSII (ΦPSII), and relative electron transfer rate at PSII (ETR) first decreased and then increased at the booting stage; Fv/Fm and ΦPSII decreased while ETR first increased and then decreased at the heading stage; nevertheless, Fv/Fm and ΦPSII first decreased and then increased but ETR was just the opposite at the maturity stage. Non-photochemical quenching coefficient (qN) and quantum yield of regulatory energy dissipation at PSII (Y(NPQ)) first increased and then decreased whereas quantum yield of non-regulatory energy dissipation at PSII (Y(NO)) first decreased and then increased at the booting, heading, and maturity stages with increasing nitrogen application rate. Photochemical quenching coefficient (qP) showed an increasing trend as the nitrogen rate increased in the range of 150-300 kg/ha at the heading and maturity stages. Photosynthetic pigments, leaf fluorescence characteristics, and yield and its components were significantly correlated. First, chlorophylls a and b were significantly negatively correlated with Fv/Fm while significantly positively correlated with qP at the heading stage. Secondly, Carotenoids were significantly positively correlated with the effective panicle number (EPN) at the booting stage while significantly negatively correlated with the spikelets per panicle (SPP) at the heading stage. Chlorophyll a and carotenoids were significantly positively correlated with EPN but significantly negatively correlated with spikelet filling (SF) at the maturity stage. In addition, qP was significantly negatively correlated with EPN at the booting stage. At the heading stage, Fv/Fm and Y(NO) were significantly negatively correlated with EPN and SPP, respectively, and Fv/Fm and ΦPSII were significantly positively related to SF. Moreover, qP was extremely significantly positively related to EPN whereas Fv/Fm was extremely significantly negatively correlated with grain yield at the maturity stage. Appropriate nitrogen application rates can enhance photosynthetic pigment contents, improve the photochemical efficiency and proportion of the open part of the reaction center of PSII, and promote the quantum efficiency and self-protection ability of PSII, thereby increasing photosynthetic efficiency and yield. Under the conditions adopted in this experiment, a parabolic relationship was observed between the nitrogen application rate and grain yield. The regression analysis results showed that the best nitrogen application rate of indica hybrid rice is 168.16 kg ha-1 and the highest yield is 11,804.87 kg ha-1.

Stability and applicability of the leaf value model for variable nitrogen application based on SPAD value in rice.

Many fertilization models have been created to scientifically determine the amount of fertilization. With the same purpose, we constructed a nitrogen (N) application model, the leaf value model, which can make N fertilizer decisions in a timely, fast and nondestructive manner during rice planting. However, only one area (A1, Jiuzhou Town, Xixiu District, Guizhou Province) and one cultivar (Qyou6) were involved in the construction of the leaf value model. Its stability and applicability could not be well evaluated. Thus, we chose another area (A2, Jiuzhou Town, Huangping County, Guizhou Province) in Guizhou Province and carried out the experiment by using four cultivars (Nie5you5399, Qyou6, Yixiangyou2115 and Zhongzheyou8) for the leaf value model construction. Compared with the average value of apparent total N uptake (Nz) obtained in 2 years in the A1 area, that in the Qyou6 leaf value model in the A2 area increased by 12%, reaching 635.72 kg ha-1, whereas the corresponding target yield changed slightly, reaching 10,999.90 kg ha-1. Simultaneously, the linear relationship between several good SPAD value-derived indexes (Ys) and apparent N supply of the field (Nx) was still significant or extremely significant in the Qyou6 leaf value model. Compared with the A1 area, it slightly differed, and the R2 of SPADL1 was higher than that of SPADL3×L4/mean. In the leaf value model of the other three cultivars, the relationship between yield and Nx and that between Ys and Nx were significant or extremely significant. The Nz of Yixiangyou2115 and Zhongzheyou8 (618.33 and 617.76 kg ha-1) were close to that of Qyou6 and the corresponding target yields were 10313.36 and 10301.99 kg ha-1, respectively. The Nz and target yield of Nie5you5399 were lowest at 546.63 and 10680.24 kg ha-1, respectively. In general, this study showed that relationships used in the construction of leaf value model had certain stability and applicability to difference areas and cultivars. The leaf value model can be considered in N fertilizer decision-making of rice planting management.

Early warning of nursing risk based on patient electronic medical record information.

In order to study the nursing risk warning of patients' electronic medical record (EMR) information, data of 200 cases of patient from Eastern Medical District of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital is selected. The Logistic regression model and nursing risk warning information system are used to calculate the death probability of the recovered patients 24h before discharge and 24h before the death of the patients. The predictive ability of the system is verified, and incidence of infusion, blood transfusion, surgical patient handover, blood sample collection nursing risk, and corresponding indirect care hours before and after the use of nursing risk warning are compared. The probability of death of the recovered patients within 24h before discharge is less than 0.5, and the death probability of the dead patients before the death of 24h is greater than 0.5. After the nursing risk warning is used, the infusion, surgical patient handover, and incidence of blood sample collection nursing risk are significantly lower than those before using the nursing risk warning and the difference is statistically significant. The indirect nursing hours of infusion, blood transfusion, surgical patient handover, and blood sample collection are significantly lower than those before using the nursing risk warning, and the difference is statistically significant. Therefore, the predictive ability of the patient's EMR information risk warning system has important reference value in clinical nursing, which can significantly reduce the incidence of infusion, surgical patient handover, and blood sample collection and nursing risk, reduce the infusion, blood transfusion, surgical patient handover, and indirect nursing hours for collecting blood samples, and improve the quality and efficiency of hospital diagnosis and treatment.

Investigation on dynamic calibration for an optical-fiber solids concentration probe in gas-solid two-phase flows.

This paper presents a review and analysis of the research that has been carried out on dynamic calibration for optical-fiber solids concentration probes. An introduction to the optical-fiber solids concentration probe was given. Different calibration methods of optical-fiber solids concentration probes reported in the literature were reviewed. In addition, a reflection-type optical-fiber solids concentration probe was uniquely calibrated at nearly full range of the solids concentration from 0 to packed bed concentration. The effects of particle properties (particle size, sphericity and color) on the calibration results were comprehensively investigated. The results show that the output voltage has a tendency to increase with the decreasing particle size, and the effect of particle color on calibration result is more predominant than that of sphericity.